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拟除虫菊酯杀虫剂氯菊酯通过 DNA 损伤和线粒体相关凋亡诱导在大鼠中引起肝毒性:罂粟的缓解作用。

The pyrethroid insecticide permethrin confers hepatotoxicity through DNA damage and mitochondria-associated apoptosis induction in rat: Palliative benefits of Fumaria officinalis.

机构信息

Laboratory of Animal Eco-Physiology, Faculty of Sciences of Sfax, University of Sfax, Sfax, Tunisia.

Laboratory of Plant improvement and Agri-Resources Valorization, National School of Engineers of Sfax (ENIS), University of Sfax, Sfax, Tunisia.

出版信息

J Biochem Mol Toxicol. 2022 Oct;36(10):e23172. doi: 10.1002/jbt.23172. Epub 2022 Jul 21.

DOI:10.1002/jbt.23172
PMID:35861702
Abstract

Permethrin (PER) is a pyrethroid pesticide that is extensively used as an insecticide in world because of its high activity and its low mammalian toxicity. The current study was conducted to investigate the protective action of Fumaria officinalis against PER-induced liver injury in male rats. However, HPLC-DAD showed the richness of 6 components in F. officinalis (F) including quercetin, ferulic acid, and naringenin which were the most abundant. Total polyphenols, total flavonoids, and condensed tannins were studied by phytochemical screening. In vitro, antioxidant properties showed that F. officinalis exhibited the highest DPPH radical, FRAP, and H O tests and total antioxidant capacity. Wistar rats were divided into four groups: negative control group (C), positive control group (F) (200 mg F. officinalis/kg BW), PER group (34.05 mg permethrin/kg BW), and PER + F group (34.05 mg permethrin/kg BW and 200 mg F. officinalis/kg BW). Oral administration of PER led to promote a decrease of body weight and Ca -ATPases and Mg -ATPases activities and an increase of plasma C-reactive protein level, transaminases, and hepatic ϒ-GT activities as well as hepatic and mitochondrial oxidative stress. An increase in plasma lactate-to pyruvate ratio and a reduction in complexes enzymes I, III, and IV activities were also observed. In addition, histoarchitecture of liver in PER-treated rats showed apoptosis and necrosis as confirmed by DNA fragmentation. F. officinalis significantly exerted hepatoprotective effect by modulating hepatic alteration and mitochondrial dysfunction as well as genotoxicity. This effect could be attributed to phenolics compounds such as polyphenols, condensed tannins, and flavonoids.

摘要

氯菊酯(PER)是一种拟除虫菊酯类农药,由于其高活性和低哺乳动物毒性,被广泛用作杀虫剂。本研究旨在探讨黄花紫堇对雄性大鼠 PER 诱导肝损伤的保护作用。然而,HPLC-DAD 显示黄花紫堇(F)中含有 6 种成分,包括槲皮素、阿魏酸和柚皮素,含量丰富。总多酚、总黄酮和缩合单宁通过植物化学筛选进行了研究。体外抗氧化性能表明,黄花紫堇在 DPPH 自由基、FRAP 和 H₂O₂测试和总抗氧化能力方面表现出最高的抗氧化能力。Wistar 大鼠分为四组:阴性对照组(C)、阳性对照组(F)(200mg 黄花紫堇/kgBW)、PER 组(34.05mg 氯菊酯/kgBW)和 PER+F 组(34.05mg 氯菊酯/kgBW 和 200mg 黄花紫堇/kgBW)。PER 口服给药导致体重下降、Ca-ATPases 和 Mg-ATPases 活性降低、血浆 C 反应蛋白水平升高、转氨酶和肝γ-GT 活性升高以及肝和线粒体氧化应激增加。还观察到血浆乳酸/丙酮酸比值升高和复合物酶 I、III 和 IV 活性降低。此外,PER 处理大鼠的肝组织学显示凋亡和坏死,这通过 DNA 片段化得到证实。黄花紫堇通过调节肝改变和线粒体功能障碍以及遗传毒性发挥显著的保肝作用。这种作用可能归因于多酚类化合物,如多酚、缩合单宁和类黄酮。

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